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Open Access Research article

Lower ribavirin biodisponibility in patients with HIV-HCV coinfection in comparison with HCV monoinfected patients

Giorgiana Hatu12, François Bailly134, Emmanuel Pourcelot5, Pierre Pradat134*, Patrick Miailhes346, Marianne Maynard134, François Parant5, Pierre Chiarello7, Jean-Michel Livrozet7, Fabien Zoulim134 and Marie-Claude Gagnieu5

Author Affiliations

1 Department of Hepatology, Hôpital de la Croix-Rousse, Hospices Civils de Lyon, 103 grande rue de la Croix-Rousse, 69004 Lyon, France

2 Université de Médicine et Pharmacie "Iuliu Hatieganu", Cluj-Napoca, Romania

3 INSERM U1052, Lyon, France

4 Université Lyon I, Lyon, France

5 Pharmacology, Hôpital Edouard Herriot, Hospices Civils de Lyon, Lyon, France

6 Departement of Infectious Diseases, Hôpital de la Croix-Rousse, Hospices Civils de Lyon, Lyon, France

7 Department of Immunology, Hôpital Edouard Herriot, Hospices Civils de Lyon, Lyon, France

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BMC Infectious Diseases 2014, 14:150  doi:10.1186/1471-2334-14-150

Published: 20 March 2014

Abstract

Background

In HIV infected patients, the impact of ribavirin (RBV) pharmacology on sustained virologic response (SVR) to hepatitis C virus (HCV) treatment has not been fully investigated. The objective of this study was to compare the early RBV plasma exposure between a population of HIV-HCV coinfected patients and an HCV monoinfected group.

Methods

Early RBV plasma exposure (expressed as Area Under the Curve (AUC) from 0 to 4 h) after a 600 mg first dose of RBV was measured in a population of HIV-HCV coinfected patients in comparison with an HCV monoinfected group. Peripheral blood samples were collected before the 600 mg RBV first dose (T0) to ensure no detectable baseline plasma RBV, and then 30 mn, 1, 2 and 4 hours after RBV intake (T0.5, T1, T2 and T4).

Results

Eighty-six patients with chronic hepatitis C entered the study among whom 23 (27%) were HIV-HCV coinfected. Coinfected patients had a significantly lower RBV-AUC 0-4h (median: 1469 μg*h/L [range 936–3677]) compared with monoinfected patients (2030 μg*h/L [851–7700]; p = 0.018). This RBV under exposure in coinfected patients persisted after normalization of AUC to RBV dose per kilogram of body weight (182 μg*h/L [110–425] versus 271 μg*h/L [82–1091], p = 0.001).

Conclusions

These results suggest that lower early bioavailability of RBV could be one of the reasons for lower SVR in HIV-HCV coinfected patients treated with pegylated interferon/RBV combination therapy. RBV plasma underexposure seems to be associated with the immunological status of the patients with lower AUC0-4h values observed in the more immunosuppressed coinfected patients.

Keywords:
Hepatitis C; Human immunodeficiency virus; Ribavirin exposure; Treatment; Coinfection